Project Summary/Abstract: High-Throughput Screening and Computational Chemistry Core (Core 1) The objective of the High-Throughput Screening and Computational Chemistry Core (HTSCC) is to contribute to the mission of the Nebraska Center for Molecular Target Discovery and Development (MTDD) by providing the critical functional infrastructure, reagents, instrumentation, technical expertise, and training necessary for MTDD investigators to conduct their research projects. By conducting high-throughput siRNA, chemical, and virtual in silico screening experiments, investigators have a novel and powerful tool to rapidly and efficiently generate accurate information about gene pathways and functions, as well as to identify small molecule inhibitors that can serve as reversible chemical probes to dissect these signaling pathways, along with the possibility of identifying lead compounds for drug discovery. These activities are generally not practical for the individual research laboratory to carry out for reasons of cost or lack of specialized technical skills and/or equipment. For MTDD investigators interested in using HTS and high-content imaging (HCI) services, the ability to add automation, miniaturize assays, and incorporate instrumentation designed for high-throughput can greatly reduce reagent, plastic-ware, and labor costs for a vast array of screening and non-screening experimentation performed in their laboratories. An additional benefit is that the scope of investigator experimentation can be greatly broadened and performed with greater precision, typically enhancing the quality and reproducibility of data. Throughout this process, on-site staff provides expertise, training, support, and feedback in the performance of screening technologies that will minimize costs, enhance throughput, and maximize the generation of interpretable results. Moreover, the core will continually develop and implement new technologies as needed and work to obtain and/or upgrade necessary instrumentation. By these means, the core will help to make MTDD investigators more competitive for research funding and to facilitate the long- term goal of performing research that ultimately results in the improvement of the health of patients.